The overall objective of this project is to understand the cellular and biochemical mechanisms which govern adrenergic neurosecretion in the iris-ciliary body. An important group of ocular hypotensive agents acts presynaptically to depress adrenergic neurotransmission in the eye. We will characterize the presynaptic receptors which modulate norepinephrine release in the isolated superfused rabbit iris-ciliary body and investigate adaptice changes in receptor responsiveness following chronic topical treatments with selective agonists and antagonists. In addition, we will study the involvement of second messengers (calcium and cyclic nucleotides) in regulation of neurosecretion and the biochemical responses to specific neuromodulators at the level of protein phosphorylation. A major goal of these studies is the identification of key regulatory steps in the neurosecretory pathway which may serve as targets for existing or novel anti-glaucoma agents.